Cells derived from transgenic mice expressing activated oncogenes offer potential as rapid and sensitive in vitro models to identify and quantify the activities of environmental chemicals that act at one or more steps in the carcinogenic process. The proposed research will focus on dermal keratinocytes isolated from two newly-developed lines of transgenic mice, HK1.ras and HK1.fos, that offer promise for the rapid and sensitive identification and quantification of epidermal carcinogens in vitro. These transgenic lines carry a fusion transgene consisting of the v-ras Ha or v-fos oncogenes, driven by the human keratin 1 (HK1) promoter, a regulatory element that limits oncogene expression exclusively to the keratinocytes. These two oncogenes operate at different stages in the process of epidermal carcinogenesis: activated ras serving as initiation event and activated fos operating at the promotional stage. The proposed research will evaluate the specificity and sensitivity of cultured keratinocytes from HSK1.ras transgenic mice for chemicals having tumor promoter activity, and cultured keratinocytes from HK1.fos transgenic mice will be used to screen chemicals for tumor initiating activity. The studies will ascertain the feasibility of developing more rapid and cost effective in vitro bioassays of carcinogens using keratinocytes from HK1.ras and HK1.fos transgenic mice. Epithelial based assays should be more relevant to the development of human carcinomas.